Transplacental induction of neurogenic tumors in BD IX rats by intragastric administration of ethylnitrosourea precursors.

The concurrent daily intragastric administration of ethylurea at two dose levels (50 mg/kg and 100 mg/kg bodyweight) together with one dose level of sodium nitrite (50 mg/kg bodyweight) by a stomach tube to pregnant BD IX rats from day 15 to day 22 of gestation resulted in the induction of neurogenic tumors in all offspring. Since both ENU-precursors alone do not produce neurogenic tumors, these results are evidence of ENU formation from its precursors under the influence of gastric juice. Differences in the survival time and the incidence of tumors at both dose levels were not significant. The amount of ethylnitrosourea synthesized in the animals was very close at both dose levels, and was dependent on the amount of sodium nitrite applied. The experimental results are consistent with the conclusion, that the rat fetuses had been exposed to a total amount of about 60 mg/kg ethylnitrosourea. Neurogenic tumors dominated with 98% incidence over the non-neurogenic. The incidence of neurogenic tumors per rat was high (6.0 for Group I and 6.7 for Group II). Neurogenic tumors were equally distributed among the central and peripheral nervous systems. The neurogenic tumors induced with the precursors of ethylnitrosourea were morphologically similar in all aspects to those induced with the carcinogen itself and could be classified as oligodendroglioma, astrocytoma, mixed glioma, anaplastic glioma, glioependymoma, ependymoma, and neurinoma. Three unusual tumors were found: one early anaplastic "septum ependymoma" in the dorsal column of the spinal cord, and two special mixed tumors of the cranial nerves, i.e. a neurinoma with portions of an oligodendroglioma and a neurinoma with parts of an invasive ependymoma.